PERSISTENT HEPATITIS-C VIRUS-INFECTION IN A CHIMPANZEE IS ASSOCIATED WITH EMERGENCE OF A CYTOTOXIC T-LYMPHOCYTE ESCAPE VARIANT
PERSISTENT HEPATITIS-C VIRUS-INFECTION IN A CHIMPANZEE IS ASSOCIATED WITH EMERGENCE OF A CYTOTOXIC T-LYMPHOCYTE ESCAPE VARIANT
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DOI：
10.1073/pnas.92.7.2755
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发表时间：
1995-03-28
影响因子：
11.1
通讯作者：
WALKER, CM
中科院分区：
文献类型：
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作者：
WEINER, A;ERICKSON, AL;WALKER, CM
丙型肝炎病毒（HCV）在人类和黑猩猩中建立了持续感染，尽管肝脏中存在病毒特异性的I类主要组织相容性复合体-限制性CD8（+）细胞毒性T淋巴细胞（ctl）。本文提供的数据表明，针对HCV非结构3蛋白中保守表位的ctl在感染慢性感染的黑猩猩的肝脏中持续存在至少2年。然而，这些ctl不能识别感染后第16周或更晚时间点存在于该动物血浆中的HCV准种。在测序的所有HCV基因组中，1449个氨基酸位置的天冬氨酸取代谷氨酸（D -> E）促进了CTL反应的逃逸。这项研究的结果有力地支持了CTL反应可以选择在宿主中持续存在能力增强的变异病毒的概念，并对HCV疫苗的设计具有重要意义。
Hepatitis C virus (HCV) establishes a persistent infection in humans and chimpanzees despite the presence of virus-specific, class I major histocompatibility complex-restricted CD8(+) cytotoxic T lymphocytes (CTLs) in the liver. The data presented here demonstrate that CTLs directed against a conserved epitope in the HCV nonstructural 3 protein persist in the liver of a chronically infected chimpanzee for at least 2 years after infection. However, these CTLs did not recognize the HCV quasi-species present in the plasma of this animal at week 16 postinfection or at later time points. Escape from the CTL response was facilitated by an aspartic acid to glutamic acid (D --> E) substitution at amino acid position 1449 in all HCV genomes that were sequenced. The results of this study strongly support the concept that CTL responses can select for variant viruses with an enhanced ability to persist in a host and have important implications for the design of vaccines against HCV.